ORGANIC LETTERS
Iron(II) Triflate as an Efficient Catalyst for the Imination of Sulfoxides
2009 Vol. 11, No. 11 2429-2432
Olga Garcı´a Manchen˜o,† Jonathan Dallimore,‡ Andrew Plant,‡ and Carsten Bolm*,† Institute of Organic Chemistry, RWTH Aachen UniVersity, Landoltweg 1, D-52056 Aachen, Germany and Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6EY, United Kingdom
[email protected] Received March 31, 2009
ABSTRACT
The challenging imination of benzyl-, sterically demanding alkyl-, and heteroaryl-substituted sulfoxides has been studied. Iron(II) triflate was identified as a highly efficient and robust catalyst for sulfur imination reactions. A variety of sulfoxides and sulfides were efficiently iminated with sulfonyliminoiodinanes (PhIdNSO2R) at room temperature to give the corresponding sulfoximines and sulfilimines in good yields and with short reaction times.
Sulfoximines can be bioactive,1 and they have been used as building blocks for the preparation of chiral ligands2 and pseudopeptides.3 A number of approaches for their synthesis have been developed, the most straightforward being direct nitrogen transfer onto the corresponding sulfoxide.4-6 Various metal-based catalysts including copper,7 rhodium,8 and †
RWTH Aachen University. Syngenta, Jealott’s Hill International Research Centre. (1) For recent examples of the patent literature related to agrochemicals, see: (a) Jeanguenat, A.; O’Sullivan, A. C. WO 032462 A1, 2006 (Syngenta). (b) Jeanguenat, A.; O’Sullivan, A. C. WO 061200 A1, 2006 (Syngenta). (c) Plant, A.; Boehmer, J. E.; Peace, A. L. WO 037945 A1, 2006 (Syngenta). (d) Huang, J. X.; Rogers, R. B.; Orr, N.; Sparks, T. C.; Gifford, J. M.; Loso, M. R.; Zhu, Y.; Meade, T. WO 2007149134 A1, 2007 (Dow Agrosciences). (e) Loso, M. R.; Nugent, B. M.; Huang, J. X. WO 2008027073 A1, 2008 (Dow Agrosciences). (f) Loso, M. R.; Nugent, B. M.; Zhu, Y.; Siddall, T. L.; Tisdell, F. E.; Huang, J. X.; Benko, Z. L. WO 2008027539 A1 (Dow Agrosciences). (g) Zhu, Y.; Loso, M. R.; Nugent, B. M.; Huang, J. X.; Rogers, R. B. WO 2008057129 A1 (Dow Agrosciences). (2) Reviews: (a) Harmata, M. Chemtracts 2003, 16, 660. (b) Okamura, H.; Bolm, C. Chem. Lett. 2004, 33, 482. (c) Bolm, C. In Asymmetric Synthesis with Chemical and Biological Methods; Enders, D., Jaeger, K.E., Eds.; Wiley-VCH: Weinheim, 2007; p 149. (d) Worch, C.; Mayer, A. C.; Bolm, C. In Organosulfur Chemistry in Asymmetric Synthesis; Toru, T., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2008; p 209. For recent examples, see: (e) Lu, S.-M.; Bolm, C. AdV. Synth. Catal. 2008, 350, 1101. (f) Lu, S.-M.; Bolm, C. Chem.sEur. J. 2008, 14, 7513. (g) Lu, S.-M.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 8920. (h) Frings, M.; Atodiresei, I.; Runsink, J.; Raabe, G.; Bolm, C. Chem.sEur. J. 2009, 15, 1566. ‡
10.1021/ol900660x CCC: $40.75 Published on Web 05/08/2009
2009 American Chemical Society
silver9 complexes have been described for this reaction.10 The use of cheap and environmentally friendly iron salts presents an attractive alternative.11 Bach and Ko¨rber reported the first iron-catalyzed sulfur imination, which employed (3) (a) Bolm, C.; Kahmann, J. D.; Moll, G. Tetrahedron Lett. 1997, 38, 1169. (b) Bolm, C.; Moll, G.; Kahmann, J. D. Chem.sEur. J. 2001, 7, 1118. (c) Tye, H.; Skinner, C. L. HelV. Chim. Acta 2002, 85, 3272. (d) Bolm, C.; Mu¨ller, D.; Hackenberger, C. P. R. Org. Lett. 2002, 4, 893. (e) Bolm, C.; Mu¨ller, D.; Dalhoff, C.; Hackenberger, C. P. R.; Weinhold, E. Bioorg. Med. Chem. Lett. 2003, 13, 3207. (4) For classical methods, see the following. NaN3/H2SO4: (a) Fusco, R.; Tenconi, F. Chim. Ind. (Milan) 1965, 47, 61. (b) Johnson, C. R.; Schroeck, C. W. J. Am. Chem. Soc. 1973, 95, 7418. (c) Brandt, J.; Gais, H.-J. Tetrahedron: Asymmetry 1997, 6, 909. O-Mesitylenesulfonyl hydroxylamine (MSH): (d) Tamura, Y.; Minamikawa, J.; Sumoto, K.; Fujii, S.; Ikeda, M. J. Org. Chem. 1973, 38, 1239. (e) Johnson, C. R.; Kirchhoff, R. A.; Corkins, H. G. J. Org. Chem. 1974, 39, 2458. (f) Tamura, Y.; Matushima, H.; Minamikawa, J.; Ikeda, M.; Sumoto, K. Tetrahedron 1975, 31, 3035. (g) Fieser, M.; Fieser, L. F. Reagents for Organic Synthesis; John Wiley & Sons: New York, 1975; Vol. 5, p 430. See also: (h) Allenmark, S.; Claeson, S.; Lowendahl, C. Tetrahedron: Asymmetry 1996, 7, 361. (5) For reviews on synthetic approaches to sulfoximines, see: (a) Johnson, C. R. Acc. Chem. Res. 1973, 6, 341. (b) Methoden Org. Chem. (Houben-Weyl); Klamann, D., Ed.; VCH Thieme: Stuttgart, 1985; Vol. E11, Parts 1 and 2. (c) Pyne, S. Sulfur Rep. 1992, 12, 57. (d) Mikolajczk, M.; Drabowicz, J.; Kielbasinski, P. In Chiral Sulfur Reagents; CRC Press: Boca Raton, 1997. (e) Taylor, P. C. Sulfur Rep. 1999, 21, 241. (f) Reggelin, M.; Zur, C. Synthesis 2000, 1. (g) Bentley, R. Chem. Soc. ReV. 2005, 34, 609. (6) For an excellent review on metal-catalyzed nitrogen transfer reactions, see: Mu¨ller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905.
FeCl2 as the catalyst.12 However, high catalyst loadings, the need for large excesses of the sulfoxide, and the use of potentially explosive BocN3 as a nitrogen source have limited the applicability of this method. Subsequently, we discovered that Fe(acac)3 conveniently catalyzes the imination of various sulfides and sulfoxides using sulfonyl amides in combination with iodosylbenzene (PhIdO).13 However, iminations of heteroaromatic substrates or sulfoxides bearing bulky substituents remained unsatisfactory.14 To overcome this limitation, the development of more efficient iron catalysts was envisaged. In the course of this search,15 we found that iron(II) triflate, which is easily prepared from iron powder or iron(II) chloride and trifluoromethanesulfonic acid,16 catalyzed the imination of thioanisole and methyl phenyl sulfoxide (1a). Using only 2.5 mol % of Fe(OTf)2, both substrates (used in 2-fold excess) reacted well with iminoiodinane (PhIdNNs) affording the corresponding sulfilimine and sulfoximine in 91% and 98% yield, respectively.17 Compared to the previously reported Fe(acac)3-based system, which required 5-10 mol % of the iron salt, this new catalyst appeared favorable.18 In order to assess the real value of these findings, an in depth investigation into the Fe(OTf)2-catalyzed sulfur imination was initiated, and the current status of this research is described here. The imination of methyl phenyl sulfoxide (1a) with PhIdNNs in the presence of 2.5 mol % of Fe(OTf)2 in (7) (a) Kwart, H.; Kahn, A. A. J. Am. Chem. Soc. 1967, 89, 1950. (b) Mu¨ller, J. F. K.; Vogt, P. Tetrahedron Lett. 1998, 39, 4805. (c) Bolm, C.; Mun˜iz, K.; Aguilar, N.; Kesselgruber, M.; Raabe, R. Synthesis 1999, 1251. (d) Takada, H.; Ohe, K.; Uemura, S. Angew. Chem., Int. Ed. 1999, 38, 1288. (e) Nakayama, J.; Otani, T.; Sugihara, Y.; Sano, Y.; Ishii, A.; Sakamoto, A. Heteroatom Chem. 2001, 12, 333. (f) Cren, S.; Kinahan, T. C.; Skinner, C. L.; Tye, H. Tetrahedron Lett. 2002, 43, 2749. (g) Lacoˆte, E.; Amatore, M.; Fensterbank, L.; Malacria, M. Synlett 2002, 116. (8) Okamura, H.; Bolm, C. Org. Lett. 2004, 6, 1305. (9) Cho, G. Y.; Bolm, C. Org. Lett. 2005, 7, 4983. (10) For alternative metal-free sulfur iminations, see: (a) Cho, G. Y.; Bolm, C. Tetrahedron Lett. 2005, 46, 8007. (b) Siu, T.; Picard, C. J.; Yudin, A. K. J. Org. Chem. 2005, 70, 932. (c) Karabuga, S.; Kazaz, C.; Kilic, H.; Ulukanli, S.; Celik, A. Tetrahedron Lett. 2005, 46, 5225. (d) Krasnova, L. B.; Hili, R. M.; Chernoloz, O. V.; Yudin, A. K. ArkiVoc 2005, iV, 268. (e) Garcı´a Manchen˜o, O.; Bistri, O.; Bolm, C. Org. Lett. 2007, 9, 3809. (11) For reviews on iron catalysis, see: (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. ReV. 2004, 104, 6217. (b) Fu¨rstner, A.; Martin, R. Chem. Lett. 2005, 624. (c) Diaz, D. D.; Miranda, P. O.; Padro´n, J. I.; Martin, V. S. Curr. Org. Chem. 2006, 10, 457. (d) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317. (e) Sherry, B. D.; Fu¨rstner, A. Acc. Chem. Res. 2008, 41, 1500. (f) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317. (g) Bauer, E. B. Curr. Org. Chem. 2008, 12, 1341. (h) Gaillard, S.; Renaud, J.-L. ChemSusChem 2008, 1, 505. (i) Correa, A.; Garcı´a Manchen˜o, O.; Bolm, C. Chem. Soc. ReV. 2008, 37, 1108. (j) Fu¨rstner, A. Angew. Chem., Int. Ed. 2009, 48, 1364. (12) (a) Bach, T.; Ko¨rber, C. Tetrahedron Lett. 1998, 39, 5015. (b) Bach, T.; Ko¨rber, C. Eur. J. Org. Chem. 1999, 64, 1033. (13) Garcı´a Manchen˜o, O.; Bolm, C. Org. Lett. 2006, 8, 2349. (14) Garcı´a Manchen˜o, O.; Bolm, C. Chem.sEur. J. 2007, 13, 6674. (15) Iron(II)/(III) perchlorates and iron(III) diketonates such as 1-acetyl2-oxo-1-cyclopentanide and 2-methyl acetylacetonate catalyzed sulfoxide iminations, but they were less efficient than Fe(acac)3. (16) (a) Haynes, J. S.; Sams, J. R.; Thomson, R. C. Can. J. Chem. 1981, 59, 669. (b) Hagen, K. S. Inorg. Chem. 2000, 39, 5867. (17) For preliminary results, see: Nakanishi, M., Dissertation, RWTH Aachen University, 2007. (18) For the application of Fe(OTf)2-based catalytic systems in nitrene transfer reactions onto enol silyl ethers and olefins, see: (a) Nakanishi, M.; Salit, A.-F.; Bolm, C. AdV. Synth. Catal. 2008, 350, 1835. (b) Mayer, A.; Salit, A.-F.; Bolm, C. Chem. Commun. 2008, 5975. For the use of related iron triflate catalysts, see: (c) Klotz, K. L.; Slominski, L. M.; Hull, A. V.; Gottsacker, V. M.; Mas-Balleste´, R.; Que, L; Halfen, J. A. Chem. Commun. 2007, 2063. 2430
acetonitrile was chosen as a model reaction (Table 1). A short optimization study of the reaction conditions showed that
Table 1. Optimization of the Fe(OTf)2-Catalyzed Imination of Methyl Phenyl Sulfoxide (1a)a entry
sulfoxide (equiv)
1 2c 3 4 5
2 1 1 1 1
PhIdX (equiv)
time (min)
yieldb (%)
PhIdNNs (1.0) PhIdNNs (1.1) PhIdNNs (1.1) PhIdNNs (1.3) NsNH2 (1.2), PhIdO (1.3)
60 30 30 30 20
98 51 66 92 85
a Reaction conditions: Sulfoxide 1a, 2.5 mol % of Fe(OTf)2, PhIdX, and MS 4 Å in acetonitrile (0.1 M) at rt. b After column chromatography. c Performed without MS 4 Å.
the sulfoxide-to-iminoiodinane ratio could be reduced (entries 2-4). However, the use of a slight excess of iminoiodinane (1.3 equiv) was required to achieve complete conversion of the sulfoxide 1a and high yields of sulfoximine 2a (entry 4). The use of molecular sieves (4 Å) also proved to be beneficial to the reaction yields (entries 2 and 3). The reactions were efficient, allowing for short reaction times (30 min). Moreover, the combination of p-nosylamide (NsNH2) and iodosylbenzene (PhIdO) to generate the corresponding iminoiodinane in situ was also effective, providing sulfoximine 2a in 85% yield after 20 min (entry 5). The use of alternative nitrogen sources to PhIdNNs was explored under the optimized conditions (Table 1, entries 4 and 5). Whereas simple amides such as BnCONH2 or CF3CONH2 with PhIdO were unreactive, a variety of iminoiodinanes (PhIdNPy and PhIdNTs) or sulfonamides (ThiophSO2NH2, BusNH2, and SESNH2) in combination with PhIdO could be efficiently employed. Thus, the corresponding N-substituted 5-methyl-2-pyridinyl- (Py), p-tolyl- (Ts), tert-butyl- (Bus), 2-thiophenyl- (Thioph), and 2-trimethylsilylethylsulfonyl (SES) sulfoximines 2b-f (Figure 1) were obtained in moderate to good yields (65-95%), offering a
Figure 1. Various products obtained in iminations of 1a. Org. Lett., Vol. 11, No. 11, 2009
Table 2. Fe(OTf)2-Catalyzed Sulfoxide Imination Scopea
c
a Reaction conditions: sulfoxide (1 equiv), Fe(OTf)2, PhIdNNs (1.3 equiv), and MS 4 Å in acetonitrile (0.1 M) at rt. b After column chromatography. Yield obtained by using 10 mol % of Fe(acac)3 as catalyst. d See ref 13. e See ref 14.
variety of possibilities for the deprotection of the sulfoximine nitrogen.19 The enhanced reactivity of this catalyst compared to previously reported iron systems12-14 was demonstrated (19) For example, nosylamides can be easily cleaved using thiolates, SES-amides react upon treatment with fluorides to give amines, tert-butyl sulfonylamides are deprotected under acidic conditions, and deprotection of the pyridinyl and thiophenyl derivatives could be achieved by reaction with Mg. For general methods for the deprotection of sulfonylamides, see: (a) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic Synthesis, 3rd ed.; John Wiley & Sons: New York, 1999; p 603. Org. Lett., Vol. 11, No. 11, 2009
by the sulfoxide imination of 1a with the bulky BusNH2, which could be performed with only 5 mol % of Fe(OTf)2 to afford the sulfoximine in 65% yield. Additionally, the use of perfluorinated alkylic sulfonamide CF3(CF2)3SO2NH2 as a nitrogen source was also possible, albeit in poor yield (20% for 2g). The unexpectedly high catalytic activity of the Fe(OTf)2based system prompted further investigation into its applicability to the imination of more challenging substrates 2431
such as sulfoxides bearing benzylic, bulky alkyl or heteroaryl substituents (Table 2). Initially, the imination of benzyl sulfoxides 1h and 1i with PhIdNNs was explored (entries 1 and 2). Whereas the use of 10 mol % of Fe(acac)3 had led to only moderate yields (46 and 44%, respectively), 5 mol % of Fe(OTf)2 was sufficiently active to drive both reactions to completion. Interestingly, and in contrast to the previously observed limitations of iron-catalyzed sulfur iminations, the presence of a coordinating substituent such as an alkoxy group (as present in 1i) did not inhibit the reaction, and both sulfoximines 2h and 2i were obtained in excellent yield (96%). The use of 5 mol % of Fe(OTf)2 was also effective in the imination of dialkyl sulfoxides with bulky isopropyl, tert-butyl, or sec-butyl substituents leading to good yields of the corresponding sulfoximines 2j-l (55-86%, entries 3-5). Iminations of sulfoxides with heteroaryl substituents were subsequently studied (entries 6-11). Benzothiazolyl- and pyridinyl-substituted sulfoxides (1m and 1n) were successfully iminated with only 5 mol % of Fe(OTf)2, while the equivalent reactions with Fe(acac)314 required 10 mol % to achieve comparable yields (83 and 80% vs 86 and 92%, respectively; entries 6 and 7). Pleasingly, the more challenging imination of oxadiazolyl sulfoxide 1o was clearly improved by use of Fe(OTf)2. When 5 mol % of this iron salt was employed, a 45% yield of sulfoximine 2o was obtained (entry 8), signifying a 2-fold improvement in yield compared to Fe(acac)3 (10 mol %).14 Increasing the catalytic loading to 15 mol % to circumvent potential deactivation of the iron catalyst by coordination to the heteroatom-containing substrate or product, afforded a 62% yield of 2o (entry 9). Even in iminations of challenging substrates bearing imidazolyl and tetrazolyl substituents (entries 10-11) remarkable yields of the corresponding heteroaromatic sulfoximines were achieved (up to 57%). Finally, the reactions of a representative array of heterocyclic sulfides, such as imidazolyl and tetrazolyl substituted substrates, were examined (Figure 2). Under the same reaction conditions as described for the iminations of heteroaromatic sulfoxides (15 mol % of Fe(OTf)2 and PhIdNNs as nitrene source), the more nucleophilic sulfides
2432
Figure 2. Heteroaryl-substituted sulfilimines 3a and 3b prepared under iron catalysis and optically active sulfoximine (R)-4 obtained from sulfoxide (R)-1r.
provided the corresponding sulfilimines 3a and 3b in good yields (63 and 66%, respectively). Lastly, the stereospecificity of the imination reaction was investigated by using optically pure (R)-methyl p-tolylsulfoxide (1r). Iron-catalyzed imination and subsequent standard nitrogen deprotection of the resulting N-nosylsulfoximine afforded enantiopure NH-sulfoximine (R)-4 in good yield (77% over two steps).20 Both the ee analysis of 4 by chiral HPLC (>99% ee) and the optical rotation revealed that the imination reaction had occurred without epimerization and retention of configuration at the stereogenic sulfur. In summary, we have demonstrated the use of Fe(OTf)2 in the preparation of challenging sulfoximines and sulfilimines with benzylic, bulky alkyl, or heteroaryl substituents. Acknowledgment. We thank the Fonds der Chemischen Industrie for financial support and Syngenta for a postdoctoral fellowship for O.G.M. Dr. Nakanishi (RWTH Aachen University) is acknowledged for the preparation of various reagents. Supporting Information Available: Experimental procedures, full characterization of new products, and copies of NMR spectra. This material is available free of charge via the Internet at http://pubs.acs.org. OL900660X (20) For experimental details, see the Supporting Information.
Org. Lett., Vol. 11, No. 11, 2009
